{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:28:46Z","timestamp":1791404926810,"version":"4.3.3"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Filarial nematodes, parasites of vertebrates, including humans, secrete immunomodulatory molecules into the host environment. We have previously demonstrated that one such molecule, the phosphorylcholine-containing glycoprotein ES-62, acts to bias the immune response toward an anti-inflammatory\/Th2 phenotype that is conducive to both worm survival and host health. For example, although ES-62 initially induces macrophages to produce low levels of IL-12 and TNF-\u03b1, exposure to the parasite product ultimately renders the cells unable to produce these cytokines in response to classic stimulators such as LPS\/IFN-\u03b3. We have investigated the possibility that a TLR is involved in the recognition of ES-62 by target cells, because phosphorylcholine, a common pathogen-associated molecular pattern, appears to be responsible for many of the immunomodulatory properties of ES-62. We now demonstrate that ES-62-mediated, low level IL-12 and TNF-\u03b1 production by macrophages and dendritic cells is abrogated in MyD88 and TLR4, but not TLR2, knockout, mice implicating TLR4 in the recognition of ES-62 by these cells and MyD88 in the transduction of the resulting intracellular signals. We also show that ES-62 inhibits IL-12 induction by TLR ligands other than LPS, bacterial lipopeptide (TLR2) and CpG (TLR9), via this TLR4-dependent pathway. Surprisingly, macrophages and dendritic cells from LPS-unresponsive, TLR4-mutant C3H\/HeJ mice respond normally to ES-62. This is the first report to demonstrate that modulation of cytokine responses by a pathogen product can be abrogated in cells derived from TLR4 knockout, but not C3H\/HeJ mice, suggesting the existence of a novel mechanism of TLR4-mediated immunomodulation.<\/jats:p>","DOI":"10.4049\/jimmunol.174.1.284","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:56:36Z","timestamp":1398027396000},"page":"284-293","source":"Crossref","is-referenced-by-count":199,"title":["Immunomodulation via Novel Use of TLR4 by the Filarial Nematode Phosphorylcholine-Containing Secreted Product, ES-62"],"prefix":"10.1093","volume":"174","author":[{"given":"Helen S","family":"Goodridge","sequence":"first","affiliation":[{"name":"Division of Immunology, Infection, and Inflammation, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fraser A","family":"Marshall","sequence":"additional","affiliation":[{"name":"Division of Immunology, Infection, and Inflammation, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn J","family":"Else","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Biological Sciences, University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina M","family":"Houston","sequence":"additional","affiliation":[{"name":"Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Egan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamyaa","family":"Al-Riyami","sequence":"additional","affiliation":[{"name":"Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foo-Yew","family":"Liew","sequence":"additional","affiliation":[{"name":"Division of Immunology, Infection, and Inflammation, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Harnett","sequence":"additional","affiliation":[{"name":"Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M","family":"Harnett","sequence":"additional","affiliation":[{"name":"Division of Immunology, Infection, and Inflammation, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,1,1]]},"reference":[{"key":"2026020212214454200_R1","first-page":"335","volume-title":"Annu. 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